Bruce Johnson (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-investigators say their findings “provide evidence to support a change in the management of patients with BRAFV600E-mutant NSCLC, a population in which additional therapeutic options are still needed.”

At a median follow-up duration of 15.9 months, 23 (64%) patients had an investigator-assessed confirmed overall response according to RECIST version 1.1. This included two (6%) patients with a complete response and 21 (58%) with a partial response.

The median response duration and progression-free survival were 10.4 and 10.9 months, respectively, while median overall survival was 24.6 months.

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Johnson et al note that the findings among this cohort are similar to those observed in an earlier cohort of the same study that only included patients with previously treated BRAF V600E-mutant metastatic NSCLC. In that group, the overall response rate was 67% and the median response duration was 9.8 months.

“These findings indicate that physicians have some flexibility to treat patients with this targeted therapy combination in either the first-line setting or following chemotherapy, and thus provide several strategies that can be considered to accommodate individual patient needs and the logistical challenges of BRAF mutation testing,” the researchers remark.

The team also notes that the safety profile of dabrafenib plus trametinib “was manageable, with no unexpected toxicities.”

The majority (69%) of patients had at least one grade 3 or 4 adverse event, most commonly pyrexia (11%), alanine aminotransferase increase (11%), hypertension (11%), and vomiting (8%), and 22% discontinued treatment due to adverse events.

In an accompanying comment, Rafael Rosell (Germans Trias i Pujol Health Sciences Institute and Hospital, Barcelona, Spain) and Niki Karachaliou (University Hospital Sagrat Cor, Barcelona, Spain) conclude that Johnson et al’s findings, combined with those from the previous two cohorts “clearly indicate that the combination of a BRAF inhibitor plus a MEK inhibitor induces significant response and benefit in progression-free survival in patients with BRAFV600E-mutant NSCLC and paves the way to further validate the combination in the frequent additional group of NSCLCs with BRAF-inactivating mutations.”